The broad aims of the proposed project are to obtain information about factors influencing synaptic organization and function in the vertebrate central nervous system. The lamprey, a jawless fish, has been chosen as the experimental animal because it has the unique property for a vertebrate of having large identifiable nerve cells and fibers which are visible in the central nervous system and permit intracellular recording. Further, the central nervous system of this animal survives well in artificial saline whose chemical composition may be varied at will. Thus, the ionic and pharmacological environment of the cells in the c.n.s. is under experimental control. Specifically, the proposed experiments are: 1) to describe the membrane effects (conductance changes, reversal potentials, ions involved, etc.) of various putative neurotransmitters when iontophoretically- and bath-applied to giant reticulospinal cells (Muller cells) and to compare the drug effects with those of the natural excitatory and inhibitory transmitters; 2) to attempt to influence the synaptic potentials evoked in Muller cells by stimulation of one cranial nerve by pairing stimulation of that input with stimulation of that input with stimulation of another ("synaptic classical conditioning"); 3) to complete an investigation of the ultrastructural correlates of "synaptic vesicle recycling" in Muller axons; 4) to attempt to produce selective uptake of horseradish peroxidase into excitatory vs. inhibitory nerve terminal endings on the cell bodies and dendrites of Muller cells; 5) to record the activity of Muller axons during natural trunk movements in intact lamprey; 6) to study the detailed pattern of synaptic activation of Muller cells by single dorsal and trigeminal sensory neurons and by other identified neural elements in the lamprey c.n.s. Efforts will be made to find identifiable neurons which make monosynaptic inputs to Muller cells.